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Associate Professor of Pediatrics Associate Professor of Human Genetics |
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| 3520A MSRB 109 Zina Pitcher Place Ann Arbor, MI 48109 -2200 |
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Our laboratory research focuses on the genetic basis of central nervous system function in relation to disorders of human development. Specifically, we focus on genes predicted to influence neuronal differentiation and migration. We are studying the roles of a transcription factor, Pitx2, and a novel chromodomain gene, Chd7, in the developing central nervous system. Pitx2 was originally identified as an important regulator of early embryonic development. Humans with mutations in PITX2 have Rieger syndrome, a genetic disorder with eye, tooth, and umbilical defects, and variable cardiac, pituitary, and brain dysfunction including mental retardation and hydrocephalus. Pitx2 is expressed in discrete regions of the brain, and is crucial for determining how these neurons become organized into functional nuclei. Chd7 is a chromodomain gene mutated in CHARGE syndrome, a congenital anomaly condition affecting the brain, eyes, ears, heart, and craniofacial structures. We use genetic approaches in mice to study how loss of Pitx2 or Chd7 disrupts organ development. These studies have important implications for understanding the mechanisms involved in central nervous system and other organ development, and for improving the diagnosis and treatment of developmental disorders.
2003 Janette Ferrantino Award, Department of Pediatrics, The University of Michigan
2004 Top 10% Teachers Award, Department of Pediatrics, The University of Michigan
2005 Ad hoc member, Developmental Brain Disorders study section (DBD), National Institutes of Health
2007 Ad hoc member, Neurogenesis and Cell Fate Study Section (NCF), National Institutes of Health
2007 Ad hoc member, Brain Disorders and Clinical Neuroscience (BDCN) Member Conflict Special Emphasis Panel, National Institutes of Health
8/83-5/87 Michigan Technological University, Houghton, Michigan, B.S. Mathematics/Foreign Language Certificate in German
6/87-6/88 Visiting Student, Universitat Stuttgart, Deutscher Akademischer Austaushdienst
8/88-12/92 The University of Michigan, Ann Arbor, Michigan, Ph.D., Neuroscience
8/92-6/96 The University of Michigan Medical School, Ann Arbor, Michigan, M.D.
8/96-7/97 Intern in Pediatrics, Mott Children's Hospital, The University of Michigan, Ann Arbor, Michigan
8/97-6/99 Resident in Pediatrics, Mott Children's Hospital, The University of Michigan, Ann Arbor, Michigan
7/99-6/01 Medical Genetics Residency, The University of Michigan, Ann Arbor, Michigan
Adams, ME, Hurd, EA, Beyer, LA, Swiderski, DL, Raphael, Y, and Martin, DM. Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: implications for human CHARGE syndrome. Journal of Comparative Neurology 504:519-532 (2007).
Skidmore, JM, Cramer, JD, Martin, JF, and Martin, DM. Cre fate mapping reveals lineage specific defects in neuronal migration with loss of Pitx2 function in the developing mouse hypothalamus and subthalamic nucleus Molecular and Cellular Neurosciences. Dec 15 (2007).
Hurd, EA, Capers, PL, Blauwkamp, MN, Adams, ME, Raphael, Y, Poucher, HK, Martin, DM. Loss of Chd7 function in gene trapped reporter mice is embryonic lethal and associated with severe defects in multiple developing tissues. Mammalian Genome, 2007 Feb;18(2):94-104 (with Cover figure).
Sclafani, AM, Skidmore, JM, Ramaprakash, H, Trumpp, A, Gage, PJ, Martin, DM. Nestin-Cre mediated deletion of Pitx2 in the mouse. Genesis, 44:336-344 (2006).
Vadlamudi, U, Espinoza, HM, Ganga, M, Martin, DM, Liu, X, Engelhardt, JF, Amendt, BA. PITX2, b-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter. Journal of Cell Science Mar 15;118(Pt 6):1129-37 (2005).
Philips, ST, Albin, RA, Martin, DM. Genetics of Subthalamic Nucleus in Development and Disease. Experimental Neurology 192 (2005) 320-330.
FJ Probst, P Hedera, AM Sclafani, MG Pomponi, G Neri, J Tyson, JA Douglas, EM Petty, DM Martin. Skewed X-inactivation in Carriers Refines Genetic Mapping of a Novel X-linked Deafness Mental Retardation Syndrome. American Journal of Medical Genetics 131A: 209-212 (2004).
Martin, DM, Skidmore, JM, Philips, ST, Vieira, C, Gage, PJ, Condie, BG, Raphael, Y, Martinez, S, Camper, SA. PITX2 is required for normal development of neurons in the mouse subthalamic nucleus and midbrain. Developmental Biology 267 (1):93-108 (2004).
Martin, DM, Skidmore, JM, Fox, SE, Gage, PJ, Camper, SA. Pitx2 Distinguishes Subtypes of Terminally Differentiated Neurons in the Developing Mouse Neuroepithelium. Developmental Biology 252(1): 84-99, 2002.
Martin, DM, Probst, FJ, Fox, SE, Schimmenti, LA, Semina, E, Belmont, JW, Camper, SA. Exclusion of PITX2 Mutations as a Major Cause of CHARGE Association. American Journal of Medical Genetics 111:27-30, 2002.
Skidmore, JM, Cramer, JD, Martin, JF, and Martin, DM. Cre fate mapping reveals lineage specific defects in neuronal migration with loss of Pitx2 function in the developing mouse hypothalamus and subthalamic nucleus. Molecular and Cellular Neurosciences 37 (2008): 696-707.
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